CPPopt: matters to be solved before or by an RCT? Geert Meyfroidt, MD, PhD Intensive Care Medicine University Hospitals Leuven Belgium

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1 CPPopt: matters to be solved before or by an RCT? Geert Meyfroidt, MD, PhD Intensive Care Medicine University Hospitals Leuven Belgium

2 Financial disclosures Research Foundation, Flanders (senior clinical investigator N)

3 Other disclosures I love ICM+ We use ICM+ daily for CPPopt guidance in TBI patients I believe that autoregulation-guided CPP management is a more rational approach than a fixed CPP threshold I believe that autoregulation changes between patients and within one patient and thus requires monitoring in the acute phase

4 My role here

5 Or maybe even worse

6 Let s hope this is not my fate

7 Track record of RCT s on neuroprotection

8 Stocchetti et al. Critical Care (2015) 19:186

9 Major problems

10 Major problems

11 Major problems What is PrX/what is CPPopt Link with physiology What happens local, what happens regional? Leuven experimental work Is PrX the best method to assess autoregulation? How does it compare to other techniques? How do we define best? Most convenient most exact most continuous best perceived best link to physiology -...? Which patients? All severe TBI? Types of injury? All intracranial hypertension? All patients who need vasopressors to maintain CPP > 50?

12 CPP MAP MAP CPP ICP MAP CPP ICP Major problems CPP = CPP = CPP? ICP CPP 70 =85-15 CPP 70 =95-25 CPP 70 =105-35

13 MAP CPP ICP CPP MAP CPP ICP MAP Major problems An ideal CPP will reduce ICP and hence change the proportion of ICP and MAP ICP Reduce MAP from 100 to 85? Maintain MAP at 100? CPP 60 =90-30 CPP 70 = CPP 85 =100-15

14 MAP CPP ICP CPP MAP CPP ICP MAP Major problems An ideal CPP will reduce ICP and hence change the proportion of ICP and MAP ICP Reduce MAP from 100 to 85? Maintain MAP at 100? CPP 60 =90-30 CPP 70 = CPP 85 =100-15

15 Major problems Which patients? All severe TBI? Which types of injury? All intracranial hypertension? All patients on vasopressors?

16 Major problems Design of the intervention? Duration? 1 week? 2 weeks? As long as sedated? As long as ICP is monitored? Until ICP control? At the preference of the treating physician? Blood pressure management after the intervention? When to change CPP target? Continuously? Hourly? times daily?

17 Major problems Design of the intervention? What is the target? Exact CPPopt? Above CPPopt? CPPopt +/- 2,5 mmhg? +/- 5 mmhg? +/- 10 mmhg? Direction of CPP? How to assess whether target was reached? During the course of the trial protocol? After trial? ITT versus per protocol?

18 Major problems Design of the intervention? How to go for CPPopt target? Vasopressors? Inotropes? Fluids? Based on what? Hemodynamic monitoring? How to avoid increasing CPP s? Tapering of CPP? Vasopressors = harmful!

19 Major problems Design of the intervention? How to go for CPPopt target? Vasopressors? Inotropes? Fluids? Based on what? Hemodynamic monitoring? How to avoid increasing CPP s? Tapering of CPP? CPP Vasopressors = harmful!

20 Major problems Design of the intervention? How to go for CPPopt target? Vasopressors? Inotropes? Fluids? Based on what? Hemodynamic monitoring? How to avoid increasing CPP s? Tapering of CPP? Vasopressors = harmful!

21 Major problems Design of the intervention? How to go for CPPopt target? Vasopressors? Inotropes? Fluids? Based on what? Hemodynamic monitoring? How to avoid increasing CPP s? Tapering of CPP? Vasopressors = harmful!

22 Major problems Control group? What if most CPPopt recommendations are between mmhg? Outcomes/endpoints? Clinical? GOS and GOSe maybe too rough Neurocognitive tests? Physiological endpoints? ICP should probably be the main endpoint: if the technique works, optimization of CPP should result in decrease of ICP Improvements in perfusion of penumbra? Multimodality monitoring?

23 ICP/CPP management is a (physiological) puzzle Vasopressors Fluid management Sedation EEG VED Osmotic therapy ICP Temperature P bt O 2 CT TCD Ventilation

24 Thank you!